Combination effect of propofol (6 mg/kg) and thiopentone sodium (8 mg/kg) administrated intravenously after premedication with xylazine hydrochloride (0.02 mg/kg) has been studied on six healthy female sheep using a crossover design. During xylazine therapy the pulse rate was significantly (P<0.01) decreased, but respiratory rate remained unchanged. The administration of anesthesia on the other hand caused a significant (P<0.01) increase in the pulse rate and a significant (P<0.01) decrease in the respiratory rate. The body temperature decreased (P<0.01) with all the three anesthetic regimens. The means of safe induction of anesthesia (propofol, 14.00 ± 0.2582; and thiopentone sodium, 14.83 ± 0.1667 seconds) and duration of anesthesia (thiopentone sodium, 14.50 ± 0.2236 and propofol, 13.22 ±0.1014 min), and a full recovery from anaesthesia (thiopentone sodium, 13.67 ± 0.4216; and propofol, 12.45 ± 0.2432 min) were differed from one another. Comparing the results of this study, it is concluded that the intravenous therapy of propofol caused a smooth quality of induction and recovery from anesthesia. Based on the measured parameters it also concludes that propofol is preferably recommended as safe therapy than thiopentone sodium for the surgical operations. Moreover, anesthetic regimens can safely be used in sheep in field as well as hospital conditions.

Article Information

Received 14 October 2016

Revised 12 January 2017

Accepted 18 March 2017

Available online 14 November 2018

Authors’ Contribution

RDB and ABK conceived and designed the experiments, performed experiments, interpreted the data and wrote the article. All other authors helped in preparation of the manuscript.

Xylazine is a thiazine derivative and acts as an agonist at the α2 class of adrenergic receptors (Bonfanti et al., 2016). Xylazine hydrochloride is clinically used for sedative, analgesic and muscle relaxant properties during minor surgical and diagnostic procedures (Clarke and Hall, 1990). Xylazine is highly lipophilic nature and directly stimulates the central α2 adrenergic receptors and leads to a decrease in neurotransmission of norepinephrine and dopamine in the central nervous system (Shi et al., 2016). In veterinary anesthesia, it is a very common procedure of combination therapy and xylazine is often used in combination with ketamine because xylazine reduces the required dose of anaesthetic. In sheep and goat, its dose ranges from 0.02 to 0.2 mg/kg (Pöppel et al., 2015). Urination following administration of xylazine is very common in sheep and goats due to lower levels of vasopressin hormone (Ghurashi, 2016). Xylazine significantly reduce the heart rate in animals and also cause hypersalivation in cattle, sheep, and goat, which is diminished by pre-treating with atropine (Giroux et al., 2015; Thanusu et al., 2010).

Propofol slows the activity of brain and nervous system and used as an injectable general anaesthetic surgery in veterinary and human medicine for the induction and maintenance of anaesthesia (Lou et al., 2015). It is a rapidly acting intravenous anaesthetic, producing anaesthesia for a short duration with rapid and smooth onset and recovery (Thompson and Godalle, 2000). A single bolus dose provides approximately 10 min of anaesthesia, with complete recovery occurring within 20 to 30 min in dogs and cats (Maney et al., 2013). Propofol at the dose rate of 5-7 mg/kg i.v. is sufficient to induce anaesthesia in sheep and goats (Kumar et al., 2014). Propofol has a fatal potential to depress respiration and to decrease blood, intramuscular and intraocular pressures. The principal site for the metabolism of propofol is the liver, whiles kidneys contribute to the extrahepatic clearance of propofol (Zonca et al., 2012).

Typically, the minor surgical procedures in sheep can be performed with physical restraint and under local sedation. Nevertheless, the major surgical problems and emergencies like dystokia, fractures, tumors, hernia, testicular abnormalities etc. may require sedation and general anaesthesia. Drugs, such as xylazine, propofol and thiopental sodium are commonly used for sedation and short duration of general anaesthesia in ruminants, including sheep. A very limited research has been done on effects of propofol and thiopentone sodium after intravenous administration. In this study evaluation of effects of propofol and thiopentone sodium in sheep sedated with xylazine hydrochloride has been investigated for the cardiorespiratory responses, including body temperature, means of induction of anesthesia, duration of anesthesia, and a full recovery from anesthesia was measured.

Materials and Methods

Animals

Six healthy adult sheep (female) with an average age of 22.67 ± 2.6 months (mean ± SE) weighing 25.83 ± 2.2kg (mean ± SE) were used in this study. Sheep were kept at Livestock Experimental Station, Faculty of Animal Husbandry and Veterinary Sciences. The animals were allowed to adapt to the surroundings for at least two weeks before experiment. All the sheep were given thorough physical examination and dewormed with Nilzan plus® (ICI). Sheep were vaccinated against enterotoxaemia and contagious pleuropneumonia (Veterinary Research Institute).

Dosage regimen and experimental design

All sheep were ear tagged with number from 1 to 6. They were fed alpha and barseem. All drugs were administered intravenously. Xylazine (Sedaziner®; Fort Dodge Animal Health, USA) at the dose rate of 0.02 mg/kg body weight was used for premedication 5 min before induction of anaesthesia. Propofol (Propofol-lipuro®; B. Braun Melsungen AG, Melsungen Germany) and thiopentone sodium (Pentothal®; Abbot,) at the dose rate of 8mg/kg and 12mg/kg, of body weight respectively were administered for induction of anaesthesia. The experimental design and assessment of anaesthetic and clinical indices were done in sheep with multimodal therapy of xylazine/propofol (treatment A) and xylazine/thiopentone sodium (treatment B) using a crossover design with at least two weeks interval between each treatments.

Experimental procedure

Before start of each experiment sheep were weighed and brought to surgery-hall for the experiment. Animals were off fed for 12 h before start of experiment. Water was available adlibitum. Wool over the left and right jugular vein was clipped with an electric hair clipper and the skin sites were disinfected with an antiseptic (tincture iodine). The sedative and anaesthetics were administered using a disposable syringe in the right jugular vein. Xylazine was injected slowly. Anaesthesia was induced with propofol and thiopental sodium given as a bolus dose (Okwudili et al., 2014).

For anaesthetic indices the degree, duration, onset of sedation and anaesthesia; nature and duration of recovery; standing time; and duration of recumbency in each animal were recorded with each treatment.

The degree of sedation was graded according to Kalhoro et al. (2010), and 0, No sedation (animal is alert); 1, Light degree of sedation (slight effect with animal becoming quieter with its head lowered below shoulder but above knee); 2, Moderate degree of sedation (animal becoming less alert, partial closure of eyelids with its head lowered below knee); 3, Deep degree of sedation (animal becoming ataxic and recumbent). The degree of anaesthesia was graded according to Verstegen et al. (1991).

Statistical analysis

The data was analysed using one way analysis of variance (ANOVA) and Tukey-Kramer Multiple Comparison test with the Graph Pad Prism 5.0 (Instant, Graph Pad Software, San Degio, USA).

Results

Pulse rate

As shown in Figure 1A, the pulse rate of all animals significantly (P<0.01) decreased after administration of xylazine. After 5 min of induction of anaesthesia pulse rateincreased significantly (P<0.01)from control and pre-induction values in all groups of treatments. The treatment A produced a maximum increase in pulse rate at 15 min, on the other hand treatment B peaked the pulse rate in 5 min only. The increased pulse rate showed a decreased trend in the pulse rate and reached the control values after 40 and 30 min with treatments A and B, respectively.

Respiratory rate

After 5 min of induction of anaesthesia, respiratory rate was significantly (P<0.01) decreased from control values up to 75 min and 90 min in treatments A and B, respectively (Fig. 1B). A maximum down-fall was occurred at 20 min in treatment A, and 10 min in treatments B and C. Later on, it was started to increase and reached the baseline values at 90 min in treatment A and at 95 min treatments B (Fig. 1B).

Body temperature

Induction of anaesthesia with propofol and thiopentone significantly decreased (P<0.01) the body temperature as compared to control value and maximum decrease occurred at 30 min with both treatments. The body temperature continued to decrease further next 20 min, 15 min and 10 min with treatment A and B, respectively (Fig. 1C).

Onset and degree of sedation

Xylazine produces signs of sedation within 56.67 ± 2.789 and 56.67 ± 2.472 seconds in treatments A and B, respectively (Fig. 2A). No recumbency was observed in all animal groups. Xylazine produced Light degree of sedation (+) in all groups.

Induction of anaesthesia

Induction of anaesthesia after administration of anaesthetic agents was 14.00 ± 0.2582 and 14.83 ± 0.1667 seconds in treatments A and B, respectively (Fig. 2B). The induction of anaesthesia was rapid (P<0.01) with propofol and thiopentone. Induction of anaesthesia with propofol and thiopentone sodium was significantly increased (P<0.01) the pulse rate from control and pre-induction values in all animals. Comparison of treatments showed that propofol caused more changes in pulse rate than thiopentone sodium. Induction of anaesthesia with propofol caused decrease in respiratory rate which remained significantly lowered (P<0.01) from control values up to 75 min, in thiopentone sodium up to 90 min. The induction of anaesthesia with propofol and thiopentone sodium significantly decreased (P<0.01) the body temperature as compared to control values.

Duration and degree of anaesthesia

The mean duration of anaesthesia after administration of propofol and thiopentone was 13.22 ± 0.1014 and 14.50 ± 0.2236 min, respectively (Fig. 2C). There were significantly difference (P<0.01) between treatment A and B, respectively. Surgical anaesthesia (stage III- plane I) was produced in all animals with all the anaesthetic regimens.

Recovery from anaesthesia

Recovery from anaestheisa was safe and excitement free with all three treatments. No any complication such as cardiac arrest, respiratory arrest, profound respiratory depression, excitement, myostitis and nerve paralysis occurred during anaesthesia and recovery period. Frequent urination, staggering, wobbling, and defecation were observed in all animals with all treatments during recovery. Recovery was smooth and all animals stood after 8.09 ± 0.4589 and 9.43 ± 0.4814 min with propofol and thiopentone, respectively (Fig. 2D).

Recovery period

The mean recovery time with treatment A and B were 12.45 ± 0.2432 and 13.67 ± 0.4216 min, respectively (Fig. 2E). Duration of recovery from anaesthesia in treatment was significantly shorter (P<0.01) than treatment A and B.

Duration of recumbency

Xylazine pre-medication not produced recumbency in all animals in all treatments. After induction of anaesthesia all the animals were recumbent. The mean duration of recumbency with treatment A and B was 25.67 ± 0.2108 and 28.17 ± 0.3073 min, respectively (Fig. 2F). There were significantly difference (P<0.01) between treatment A and B.

Other observations

Together with above mentioned anaesthetic indices with the multimodal therapy of drugs, several other effects were observed such as wobbling, head drooping, and no recumbency were observed in all animals with xylazine administration. Apnoea was predominantly more prolonged after induction of propofol anaesthesia than with other two treatments. The palpebral reflex, pedal reflex, swallowing reflex, jaw tone, movement of limbs and tail were absent in all animals after administration of all three anaesthetic regimens, while nystagmus, corneal reflex, snoring, arrhythmias, anal relaxation, muscle relaxation, protrusion of tongue, jugular pulsation, frequent urination, tympany were observed in all animals with all treatments. Moreover, the muscle relaxation with treatments A is more pronounced than treatment B.

Discussion

Rapid and smooth induction of anesthesia is desirable in ruminants in field as well as hospital conditions. The present study was carried out to study and compare efficacy of bolus doses of two rapidly acting intravenous anesthetics (propofol: 6 mg/kg and thiopentone sodium: 8 mg/kg) preceded by intravenous administration of xylazine (0.02 mg/kg) as pre-medication in six sheep under same experimental conditions.

Administration of xylazine significantly decresased (P< 0.01) the pulse, respiratory rates and body temaperature. Significant decrease in pulse and not respiratory rates after pre-anaesthetic administration of alpha2-agoinst have been reported by other researchers in sheep (Mather et al., 2004) and in goats (Shi et al., 2016). Significant changes in the body temperature after xylazine administration in sheep have also been reported by others in sheep and in goats (Okwudili et al., 2014). However, significant decrease in rectal temperature has been reported in buffalo calves (Runciman et al., 1990).

Based on the results from this study, xylazine (0.02 mg/kg) pre-treatment produced satisfactory sedation in sheep and induced the duration of anaesthesia for conducting minor surgical procedures without any serious side effect like cardiac arrest or respiratory arrest. Intravenous administration of propofol and thiopentone sodium as bolus doses produced rapid, safe and excitement free induction of anaesthesia. All anaesthetic regimes produced sufficient duration of anaesthesia for conducting minor short duration surgical procedures without any serious side effects. Considering the parameters measured, propofol is graded superior than thiopentone sodium because of smoother and fast induction of anesthesia and a long length recovery from anaesthesia.